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Tumor protein 53 mutations mapping to its tertiary structure with in-silico prediction of neoepitopic vaccine candidates in bone tumors
Hamid Nawaz Tipu and Abdul Rehman Arshad

Mapping of tp 53 mutations in bone cancers present in COSMIC database to its secondary and tertiary structure with in silico prediction of newly formed HLA binding epitopes as candidates for synthetic peptide vaccine. Mutations in bone cancers present in COSMIC database were listed and manually induced in wt p53 FASTA sequence. Wt p53 secondary structure was predicted. Template identified and tertiary structure of wt p53 was modelled in Cn3D followed by individual mutations mapping onto this model. HLA class I binding affinity was determined for mutated sequences to determine any newly binding peptide sequences. 62 missense mutations were identified. After predicting secondary structure, template was identified as PDB ID 1MZR for tertiary structure modelling. Mutations were highlighted that showed most of mutations in DNA binding region of tp 53 tetramer. Wt p53 had 19 HLA class I binders whereas in 62 mutated sequences we identified 18 neobinders not present in wt sequence. Neoepitopes identified serve as candidates for individualized anti-cancer peptide vaccine therapy.

Keywords: Immunoinformatics, bone tumors, tumor protein 53, human leukocyte antigen, in-silico prediction.

Abbreviations: Tumor protein 53 (p53), human leukocyte antigen (HLA), wild type sequence (wt).

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